Changes in Hb level, markers of hemolysis, biochemical parameters, RBC parameters of functional assays, and markers of SCD-related complications from baseline to the end of the dose-finding period and mean of the fixed-dose extension period (intention-to-treat analysis)
| . | Baseline (n = 9) . | End of the dose-finding period (n = 9) . | Mean of the fixed-dose extension period (n = 9) . | P (baseline vs mean of the fixed-dose extension period) . |
|---|---|---|---|---|
| Hb level and markers of hemolysis | ||||
| Hb, g/dL | 8.8 (1.8) | 10.3 (1.3) | 9.9 (1.8) | .0014 |
| Reticulocytes | ||||
| ARC, 109 per L | 235 (88) | 141 (50) | 156 (50) | .0038 |
| % of RBCs | 8.2 (2.3) | 4.2 (1.4) | 5.0 (1.4) | .0003 |
| Total bilirubin, mg/dL | 2.6 (1.3) | 1.2 (0.5) | 1.4 (0.7) | .0025 |
| LDH, U/L | 500 (307) | 328 (113) | 401 (224) | .0217 |
| Biochemical parameters | ||||
| ATP, mg/gHb | 2.9 (0.7) | 3.6 (0.5) | 3.6 (0.5) | .1386 |
| 2,3-DPG, mg/gHb | 11.4 (1.0) | 7.9 (1.1) | 9.0 (1.1) | .0004 |
| ATP:2,3-DPG ratio | 0.25 (0.05) | 0.46 (0.09) | 0.40 (0.06) | .0009 |
| RBC parameters of functional assays | ||||
| PoS, mmHg | 40.2 (8.8)∗ | 33.1 (9.7)∗ | 36.2 (6.3)∗ | .0802 |
| EImax, EI | 0.450 (0.074)∗ | 0.477 (0.059)∗ | 0.478 (0.061)∗ | .0017 |
| EImin, EI | 0.067 (0.048)∗ | 0.116 (0.049)∗ | 0.101 (0.066)∗ | .0054 |
| P50, mmHg | 24.0 (2.4) | 21.5 (1.4) | 22.5 (1.8) | .0032 |
| Markers of SCD-related complications | ||||
| Annualized VOE rate Dose-finding period + fixed-dose extension period† Fixed-dose extension period | 1.33 (1.32) | 0.64 (0.87) | .0489† | |
| 0.72 (2.17) | 0.60 (0.78) | .0625 | ||
| Annualized SCD-related hospital admission days | 5.3 (7.0) | 0.0 (0.0) | 4.1 (5.6) | .4452 |
| . | Baseline (n = 9) . | End of the dose-finding period (n = 9) . | Mean of the fixed-dose extension period (n = 9) . | P (baseline vs mean of the fixed-dose extension period) . |
|---|---|---|---|---|
| Hb level and markers of hemolysis | ||||
| Hb, g/dL | 8.8 (1.8) | 10.3 (1.3) | 9.9 (1.8) | .0014 |
| Reticulocytes | ||||
| ARC, 109 per L | 235 (88) | 141 (50) | 156 (50) | .0038 |
| % of RBCs | 8.2 (2.3) | 4.2 (1.4) | 5.0 (1.4) | .0003 |
| Total bilirubin, mg/dL | 2.6 (1.3) | 1.2 (0.5) | 1.4 (0.7) | .0025 |
| LDH, U/L | 500 (307) | 328 (113) | 401 (224) | .0217 |
| Biochemical parameters | ||||
| ATP, mg/gHb | 2.9 (0.7) | 3.6 (0.5) | 3.6 (0.5) | .1386 |
| 2,3-DPG, mg/gHb | 11.4 (1.0) | 7.9 (1.1) | 9.0 (1.1) | .0004 |
| ATP:2,3-DPG ratio | 0.25 (0.05) | 0.46 (0.09) | 0.40 (0.06) | .0009 |
| RBC parameters of functional assays | ||||
| PoS, mmHg | 40.2 (8.8)∗ | 33.1 (9.7)∗ | 36.2 (6.3)∗ | .0802 |
| EImax, EI | 0.450 (0.074)∗ | 0.477 (0.059)∗ | 0.478 (0.061)∗ | .0017 |
| EImin, EI | 0.067 (0.048)∗ | 0.116 (0.049)∗ | 0.101 (0.066)∗ | .0054 |
| P50, mmHg | 24.0 (2.4) | 21.5 (1.4) | 22.5 (1.8) | .0032 |
| Markers of SCD-related complications | ||||
| Annualized VOE rate Dose-finding period + fixed-dose extension period† Fixed-dose extension period | 1.33 (1.32) | 0.64 (0.87) | .0489† | |
| 0.72 (2.17) | 0.60 (0.78) | .0625 | ||
| Annualized SCD-related hospital admission days | 5.3 (7.0) | 0.0 (0.0) | 4.1 (5.6) | .4452 |
Data are presented as mean (standard deviation). P values derived from paired sample t test or Wilcoxon signed-rank test when appropriate to compare baseline values with the mean values of the fixed-dose extension period (unless otherwise stated), but not with the mean values of the end of the dose-finding period (in italics).
ARC, absolute reticulocyte count.
Due to technical issues of the oxygen gradient ektacytometer, data are missing for 1 patient a week 52 visit (n = 1 patient), and 4 visits from week 24 to week 52 in the fixed-dose extension period (n = 2 patients).
Intention-to-treat analysis of baseline vs the total period on study drug treatment (the dose-finding period and the fixed-dose extension period combined) instead of only the fixed-dose extension period.